OBJECTIVE: To investigate the difference of heart rate variability (HRV) and serum creatine kinase isoenzyme (CK-MB) activity between right-sided and left-sided stroke, and the relative impact of cardiac autonomic imbalance and heart abnormality on death by serum CK-MB activity and fractal dimension (FD) detection in patients with stroke. METHODS: Three hundred and twenty-seven patients (mean age: 61.12 +/- 9.74 years) with an acute first-ever stroke underwent a comprehensive clinical investigation and laboratory tests, and were followed up for 1 month. Serum CK-MB activity and FD of heart rate variability were detected on the next day after admission. RESULTS: During the 1 month follow-up period, 42 out of 327 (12.84%) patients had died. Among all the variables analysed, FD decreased and serum CK-MB activity increased after stroke, and decreased FD was more common in the right-sided stroke. This study also demonstrated that acute phase increased serum CK-MB activity [odds ratio (OR)=0.226, 95% CI: 0.103-0.493, p= 0.000) and decreased FD (OR=0.276, 95% CI: 0.135-0.567, p=0.000) had been linked with the risk of death. CONCLUSIONS: Right-sided stroke and left-sided stroke had different influences on cardiac autonomic nerve activity. Acute phase increased serum CK-MB activity and decreased FD are well-established prognostic factors of death in patients with stroke. Assessment of FD and serum CK-MB activity may provide additional information on the risk of death in stroke patients.